The objective of our research program is to search for unique characteristics of human biology which determine their extraordinary capacity for general health maintenance and longevity as compared to all other mammalian species. This research program has been guided by theoretical studies suggesting that a common set of specific longevity determinant processes exists in all mammals. Work has centered on two basic but interrelated questions: (1) is the cause of aging largely the result of dysdifferentiative processes and (2) is the rate of aging governed by mechanisms acting to stabilize the proper differentiated state of cells? With reference to the first question, stability of gene regulation has been investigated by measuring the steady state levels of MRNA for the genes coding for the endogenous retroviruses (human 4-1, mouse MuLV), oncogene (c-Wc) and satellite heterochromatin DNA as a function of age in a number of tissues from mice and human. Recent studies of the possible age-dependent expression of mouse satellite DNA sequences show that (1) such DNA sequences do become expressed in mammalian species, (2) such expression is highly tissue-specific, being found only in heart tissue in C57BL/6J mice, and (3) expression is correlated with age of the mice, increasing in a linear manner through life span. Expression of human 4-1 endogenous retrovirus in liver and kidney tissues have now been confirmed using in situ hybridization studies. Expression in both tissues is highly localized within hot-spot clusters of cells.